tbuckley/cabot-search huggingface dataset:
Randomized controlled trial of the efficacy of lymph node dissection on stage IIICr of cervical cancer (CQGOG0103).
Authors: Misi He, Lin Zhong, Haixia Wang, Ying Tang, Qi Zhou, Dongling Zou
Journal: Journal of Clinical Oncology (2022)

TPS5604 Background: In FIGO 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopically positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. No prospective study reported that resecting macroscopic nodes before Concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer. The CQGOG0103 study is a national, prospective, multicenter and randomized clinical study evaluating lymph node dissection on stage IIICr of cervical cancer. Methods: Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by CT/MRI/PET/CT) and the short diameter of image-positive lymph node ≥15mm. 452 patients will be equally randomized to receive either CCRT (Pelvic EBRT/Extended-field EBRT + cisplatin (40mg/m2) or carboplatin (AUC = 2) every week for 5 cycles + brachytherapy) or Open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. The sample size calculation of 346 patients provides 80% power to detect a difference in survival at the two-sided 5% significance level using the log-rank test, considering a 20% reduction, a total of 452 patients are required. This study began in January 2021 and will be accrued within 4 years. Enrollment is ongoing.
INSP-06. Recent advances in improving neuropsychological outcomes for paediatric brain tumour patients - Are we entering a new era?
Authors: Donald Mabbott
Journal: Neuro-Oncology (2022)

Abstract Children and youth treated for brain tumours can sustain a brain injury as a consequence of the tumour and curative therapy leaving them with significant cognitive challenges. Advances in treatment for paediatric brain tumours – particularly the delivery of radiotherapy – have been associated with improved neuropsychological outcome in survivors, however. This presentation will first focus on work documenting the impact of changes in cranial radiotherapy delivery and modality on neuropsychological late effects in children treated for medulloblastoma. Outcomes in patients treated on modern protocols are substantially improved relative to prior therapy, however challenges remain. Second, novel approaches for cognitive recovery and brain repair in survivors of paediatric brain tumours will be discussed, with a focus on novel approaches for fostering endogenous neuroplasticity for cognitive recovery and brain repair in children and youth treated for paediatric brain tumours.
LGG-14. LOGGIC (Low Grade Glioma in Children) Core BioClinical Data Bank: Establishment and added clinical value of an international molecular diagnostic registry for pediatric low-grade glioma patients
Authors: Emily C Hardin, Simone Schmid, Alexander Sommerkamp, Michè le Simon, Claudia Caspar, Carina Bodden, Anna-Elisa Heipertz, Philipp Sievers, Andrea Wittmann, Ashwyn A Perera, Till Milde, Stefan M Pfister, Andreas von Deimling, Pablo Hernáiz Driever, Arend Koch, Darren Hargrave, Olaf Witt, David Capper, Felix Sahm, David T W Jones, Cornelis M van Tilburg
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data. In addition to routine histopathological and molecular analyses, LOGGIC Core determines the driver alteration as precisely as possible to support treatment decisions and participation in interventional trials. Hence, the question arises whether comprehensive implementation of RNA sequencing using Fresh Frozen (FF) tumor tissue to identify underlying gene fusions improves diagnostic accuracy and provides a clinical benefit. METHODS: Establishment of an international molecular and clinical registry including the logistical and analytical pipeline. First analysis of all patients age 0 to 18, which were included in Germany as part of the German HIT-LOGGIC-program between April 2019 and February 2021, and for whom FF tissue was available. This included histopathological evaluation, immunohistochemistry, 850k methylation analysis, gene panel sequencing, RNA sequencing using FF tissue. RESULTS: FF tissue was available in 178/379 included cases. RNA sequencing was performed on 125 samples. In this prospective, population based cohort, we confirmed KIAA1549:BRAF-fusion (57%), BRAFV600E-mutation (9%) and FGFR1-changes (10%) as most frequent alterations. 12% of cases presented rare gene fusions (e.g. TPM3:NTRK1, EWSR1:VGLL1, GOPC:ROS1, SH3PXD2A:HTRA1, PDGFB:LRP1). In 19% of cases, RNA sequencing detected an actionable target not identified by conventional methods. CONCLUSION: The addition of RNA sequencing reveals clinically relevant alterations including rare gene fusions. By demonstrating improvement of diagnostic accuracy and making precision oncology studies (MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible, the added value for pLGG patients becomes apparent. LOGGIC Core is currently being rolled out internationally and aims to define the new state of the art standard molecular diagnostics. We propose to include RNA sequencing as part of routine diagnostic procedures for all pLGG patients, especially in tumors where no common MAPK alteration was identified.
Association of Mistreatment and Discrimination With Medical School Attrition
Authors: Mytien Nguyen, Sarwat I. Chaudhry, Mayur M. Desai, Candice Chen, William A. McDade, Tonya L. Fancher, Dowin Boatright
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Efficacy and safety in advanced hepatocellular carcinoma using atezolizumab plus bevacizumab combined with interventional therapy: A retrospective analysis of real-world evidence.
Authors: Jiamin Cheng, Bowen Chen, Yi Jing, Yinying Lu
Journal: Journal of Clinical Oncology (2022)

e16112 Background: Recently, atezolizumab plus bevacizumab (A+T) has shown promising effects on hepatocellular carcinoma (HCC). So far, no study explored the effectiveness and safety of A+T combined with interventional therapy in patients with HCC. This study aimed to explore short-term efficacy and safety of A+T combined with interventional therapy in first-line treatment of advanced HCC. Methods: In this retrospective study, 13 advanced HCC patients received first-line A+T combined with interventional therapy from September 2020 to September 2021 were enrolled. Liver function was evaluated by Child-Pugh score. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and adverse events (AEs) were recorded in accordance with RECIST v1.1 and CTCAE v5.0. The PFS was defined as the time from first dosing of A+T or first time of interventional therapy until disease progressive or death. Results: A total of 13 HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage C were reviewed. The liver function of 8 patients was Child-Pugh A while the other 5 patients was Child-Pugh B. Median time of following up was 8.9 (5.2-12.6) months. The ORR and DCR were 30.8% and 84.6%, respectively. One patient was able to conduct hepatectomy after treatment. And CR was confirmed by pathological report after surgery. The median PFS was 9.7 (7.3-12.1) months. The 3-month PFS rate was 84.6%. Nearly all patients suffered from AEs. The most frequency AE were hyperthyroidism (6 of 15), following hypertension (4 of 15), weight loss (4 of 15). While platelet-cell- decrease (3 of 15) turn out to be the most frequent serious AE, but it could be well managed. No AE-related death happened. Total two patients died, of progression of tumor and septic shock respectively. Conclusions: A+T combined with interventional therapy showed potential short-term anti-tumor effect and tolerance on advanced HCC.[Table: see text]
GCT-20. Multi-Institutional Analysis of Pediatric Relapsed/Refractory Central Nervous System Germ Cell Tumors
Authors: Sumanth Nagabushan, Girish Dhall, Mohamed Abdelbaki
Journal: Neuro-Oncology (2022)

Abstract Central nervous system (CNS) germ cell tumors (GCTs) constitute ~ 4% of primary pediatric brain tumors in the United States. While multimodality therapy approaches have ensured &amp;gt;80% survival benefit, these patients still experience relapses, with no established standard of care. Their rarity limits knowledge of their outcomes and associations with location, metastatic status, impact of surgery, serum, and cerebrospinal fluid (CSF) biomarkers, to only a few smaller trials and case series.This international multi-institutional retrospective study for relapsed/refractory germinomas and NGGCTs, will evaluate the association between different treatment modalities and 5-year OS and EFS; patterns of relapse, including along biopsy tracts; and potentially identify predictors of recurrence. De-identified patient data at primary and relapse time points will be collected focusing on treatment approaches such as surgery, conventional/high dose chemotherapy, photon/proton radiation therapy; timing and site of relapse; imaging characteristics and serum/CSF biomarkers (BHCG/AFP). Our collaborators include multiple sites across North America, Australia, Europe, Africa, South America, the Middle east, India, Singapore, and Malaysia. 6 recurrent intracranial germinomas on the CBTN (Children’s Brain Tumor Consortium) database were assessed, demonstrating a male gender preponderance (4) and recurring in the suprasellar region (3), frontal lobe (2) and spinal cord (1). 2 underwent gross total resection while 1 had biopsy only. Conventional or high-dose chemotherapy was administered in 5, while 2 received craniospinal and 1 proton radiation. 4 patients are alive. Median OS was 738 days and EFS 1093 days. However, biomarker (AFP/BHCG) data was unavailable. Updated results will be presented at the conference. With global partnership and contribution, we anticipate this study to help bridge existing gaps in our knowledge of this rare patient cohort and establish a consensus standard of care, through prospective clinical trials in the future. We acknowledge the CBTN for kindly providing data access.
Searching for cardioprotective microRNA families by bioinformatics analysis of cross-species transcriptomic datasets
Authors: B Agg, B Benczik, BV Kemendi, A Makkos, M Petervari, ZV Varga, P Ferdinandy
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the National Research, Development and Innovation Office of Hungary (NKFIA; NVKP-16-1-2016-0017 National Heart Program) and the Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Molecular Biology thematic programmes of the Semmelweis University. Introduction There is a growing body of evidence that changes in cardiac microRNA expression pattern plays an important role in cardioprotective cellular signaling. Purpose Our aim was to identify evolutionarily conserved cardioprotective microRNA (protectomiR) families with a high probability of translation into human clinical practice. Methods Global cardiac microRNA expression profiles were measured in both a rat and a porcine model of myocardial infarction with or without ischemic preconditioning and postconditioning by microarray and high-throughput polymerase chain reaction, respectively. A software developed by our team was used to identify cross-species microRNA families (i.e. microRNAs with identic seed sequence) with cardioprotective expression patterns. By selecting experimentally validated human target genes from the miRTarBase database we built a microRNA family-target interaction network by the miRNAtarget.com software. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the selected target genes. Results Due to potential patenting, microRNAs and microRNA families were anonymized. We identified 7 microRNA families, showing cardioprotective expression pattern. Based on the analysis of the microRNA family-target network, expression change of the target hubs were predicted to be consistent with previously described changes in pathways with high relevance in cardioprotection (e.g. positive regulation of TGF-beta, HIF-1, PI3K-Akt signaling pathways). Conclusion By an unbiased transcriptomics and bioinformatics based approach we successfully identified microRNA families with robust cross-species protectomiR expression pattern and targets involved in well-established cardioprotective pathways. These cardioprotective microRNA families are of high translational value for human clinical application.
Financial payments from the pharmaceutical industry to U.S. cancer centers, 2014-2019.
Authors: Aaron Philip Mitchell, Meredith Brown, Niti U. Trivedi, Peter Brian Bach
Journal: Journal of Clinical Oncology (2022)

1582 Background: Payments from the pharmaceutical industry to US health care providers were made public through Open Payments in 2013. Since then, industry payments to individual physicians have been studied extensively, but payments to hospitals remain uncharacterized. The goal of this study was to examine trends in industry payments to US cancer centers. Methods: We identified all US cancer centers that were National Comprehensive Cancer Network (NCCN) members or were National Cancer Institute (NCI) comprehensive cancer center as of 2019. Each institution was manually mapped to Open Payments, which contains industry payment data. Where applicable, subsidiary hospitals were included with the parent center. Among the NCCN centers, we used National Plan and Provider Enumeration System data to identify medical oncologists practicing there. Oncologists were linked to Open Payments by name and address. We analyzed “research payments” (RP), which include payments related to preclinical and clinical research, and “general payments” (GP), which include non-research-related payments in categories such as speaker fees, consulting fees, meals, grants, charitable contributions, and licensing fees. We ascertained public research support from NIH data, and included all research project grants. We used correlation analysis and linear regression models to assess the association between industry payments to a cancer center and to oncologists practicing at that center. All dollar values were inflation-adjusted to 2019 dollars using the Consumer Price Index for medical care from the US Bureau of Labor Statistics. Results: Overall industry RP to US cancer centers increased from $527 million in 2014 to $653 million in 2019, while GP increased from $346 million to $786 million. NCI research funding increased from $1,397 million in 2014 to $1,583 million in 2019 (13.3% increase) while overall industry payments (RP+GP) increased from $873 million to $1,439 million (64.8% increase). Industry payments were highest as a portion of total income (industry + NCI) at MD Anderson (64.2%) and lowest at St. Jude (0.1%). Among NCCN institutions, industry payments to cancer centers and the oncologists practicing at those centers were correlated (coefficient = 0.382). A $1,000 increase in GP to a cancer center from a given pharmaceutical company was associated with a $1.00 ($0.61 - $1.30) increase in GP from that company to oncologists at that cancer center. Conclusions: From 2014-2019, cancer center funding from industry sources grew quickly, driven by an increase in non-research payments, and now approaches the amount of public research funding cancer centers receive. Cancer center acceptance of industry payments is associated with increased industry payments to its employed physicians, which are known to sway prescribing practices. These trends raise concerns regarding the ability of these institutions to fulfill their public missions.
The association between pre-exposure to glucocorticoids and other immunosuppressant drugs with severe COVID-19 outcomes
Authors: Rakel Brodin, Suzannes Desirée van der Werff, Pontus Hedberg, Anna Färnert, Pontus Nauclér, Peter Bergman, Ana Requena-Méndez
Journal: Clinical Microbiology and Infection (2022)

Whether preinfection use of immunosuppressant drugs is associated with COVID-19 severity remains unclear. The study was aimed to determine the association between preinfection use of immunosuppressant drugs with COVID-19 outcomes within 1 month after COVID-19 diagnosis.This cohort study included individuals aged ≥18 years with underlying conditions associated with an immunocompromised state and diagnosed with COVID-19 between February 2020 and January 2021 at Karolinska University Hospital, Stockholm. Exposure to immunosuppressant drugs was defined based on dose and duration of drugs (glucocorticoids and drugs included in L01 or L04 chapter of Anatomical Therapeutic Chemical classification) before COVID-19 diagnosis. Outcomes included hospital admission, ICU admission, mechanical ventilation, mortality, renal failure, stroke, pulmonary embolism, and cardiac event. ORs were calculated using logistic regression and baseline covariate adjustment for confounding with inverse probability of treatment weights.Of 1067 included individuals, 444 were pre-exposed to immunosuppressive treatments before COVID-19 diagnosis (72 high-dose glucocorticoids, 255 L01 drugs (antineoplastics), 198 L04 (other immunosuppressants) and 78 to multiple drugs). There was no association between pre-exposure and hospital admission (OR 0.83, 95% CI 0.64 to 1.09) because of COVID-19. Pre-exposure to L01 or L04 drugs were not associated with hospital admission (adjusted ORs (aORs): 1.23, 0.86 to 1.76 and 1.31, 0.77 to 2.21) or other outcomes. High-dose glucocorticoids (≥20 mg/day prednisolone equivalent) were associated with hospital admission (aOR 2.50, 1.26 to 4.96), cardiac events (aOR 1.93, 1.08 to 3.46), pulmonary embolism (aOR 2.78, 1.08 to 7.15), and mortality (aOR 3.48, 1.77 to 6.86) due to COVID-19.Antineoplastic and other immunosuppressants drugs were not associated with COVID-19 severity whereas high-dose glucocorticoids were associated. Further studies should evaluate the effect of pre-exposure of different dose of glucocorticoids on COVID-19 prognosis.
QOL-22. Neurocognitive performance in survivors of pediatric brain tumors with neurocutaneous syndromes
Authors: Ingrid Tonning Olsson
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Pediatric brain tumors (PBT) in children with neurocutaneous syndromes are typically low-grade and survival rates are close to 100%. Neurocutaneous syndromes are associated with neurocognitive and behavioral problems, and a diagnosis of brain tumor adds to the total neurocognitive burden. The aim of this study was to describe neurocognitive performance in survivors of PBT with a neurocutaneous syndrome and to find associated factors. METHOD: Neurocognitive data (verbal and non-verbal reasoning, cognitive processing speed, working memory, and executive function) on 20 survivors of brain tumors with neurocutaneous syndromes were collected from medical logs. Results were converted to z-scores (m=0, sd=1) using age-adjusted national norms. Generalized linear models were built to find factors associated with neurocognitive performance. Most survivors had received several assessments and all assessments were added to the model together with time since diagnosis at assessment. RESULTS: Seventeen of the survivors (85%) had undergone 1-3 assessments and 3 survivors had undergone 4-5 assessments. Six survivors (30%) had a diagnosis of intellectual disability, and neurocognitive scores were low at all assessment points: average z-score across all datapoints(sd): verbal reasoning -1.1(1.2); non-verbal reasoning -1.2(0.9); working memory -1.9(0.7); cognitive processing speed -1.0 (1.0); executive function -0.6 (1.0)). Factors associated with worse neurocognitive performance were young age at brain tumor diagnosis, larger tumors, epilepsy, and longer time span between diagnosis and assessment. CONCLUSIONS: Survivors of PBT with neurocutaneous syndromes are at risk for neurocognitive deficits that might worsen over time. These survivors need personalized neurocognitive follow-up. When examining neurocognitive performance and associated factors in survivors of PBT special consideration needs to be taken to survivors with neurocutaneous syndrome since these survivors receive limited cancer treatment and still have neurocognitive deficits.